ABSTRACT This is an application for a K24 award for Dr. Lea T. Grinberg, a neuropathologist at the University of California, San Francisco (UCSF). Dr. Grinberg is an Associate Professor in Residence and co-lead the UCSF/Memory and Aging Center's Neuropathology Core. She is an established researcher in the patient- oriented clinical research of dementia. A distinctive hallmark of her research is her direct involvement in creating, managing and analyzing well-characterized postmortem collections of brains belonging to people at- risk or already with dementia. Dr. Grinberg proposes to use K24 dedicated time to mentor USCF as well as international investigators in patient-oriented dementia research. Her mentees will gain hands-on research experience, expertise in age-related human neuropathology, training in data analysis, manuscript preparation, and grant writing, as well as career, mentoring. Mentee training will leverage the infrastructure and resources of the UCSF/Memory and Aging Center Autopsy program, which is part of ongoing longitudinal cohort studies (P50AG02350 and P01AG019724), and her collaborations with multidisciplinary researchers in the areas of dementia domestically and worldwide. To increase her mentoring skills, she proposes to participate in the UCSF Mentor Development Program. Dr. Grinberg intends to conduct K24-supported Alzheimer's disease research studies that will serve as training vehicles for mentees and expand her research. These studies, using clinical, genetic and neuropathological data, will be conducted using data from ongoing UCSF/Memory and Aging Center's NIH-funded cohort studies of persons with Alzheimer's disease(AD) . She will examine the role of recently described neurodegenerative changes in modifying the clinical phenotype of AD. In summary, this K24 will enhance Dr. Ginberg's active research program with extensive infrastructure at UCSF to support her goal to remain a leader in neurodegenerative diseases, especially in the field of neuropathology, and to develop a program of excellence for training medical students, trainees, and junior faculty in POR related to age-related neuropathology that is also intended to close the gaps caused by interruption of neuropathology training for neurologists and neurodegenerative disease training for neuropathologists.